Experimental studies are in progress to determine the relative efficacy of low levels of hyperthermia for short time periods (e.g., 40-42 degrees C for times up to 4-6 hours) to inactivate hypoxic and aerobic cells of normal and malignant origin by in vivo and in vitro techniques. Our available data strongly indicate that hypoxic cells are quite sensitive to this level of hyperthermia. Kinetics of repair of thermal damage, modification of response of tissue to ionizing radiation, effect of fractionated thermal and radiation exposures. Experimental animal tumor systems to be employed: mammary carcinoma, fibrosarcoma, and squamous cell carcinoma. In vitro work will be based upon chinese hamster, HeLa, human glial cells (normal and malignant). The study to determine dependence of tissue response of dose per fraction and the point at which decreases in dose per fraction renders fractionated irradiation comparable in effectiveness to low dose rate continuous irradiation (approximately 0.5 Do/hr). An analysis of recurrence time distribution of mammary carcinoma and fibrosarcoma is in progress; specific point of interest is appearance of late recurrences, i.e., later than 600 days. With our animals mean survival times will be approximately 900 days. In some earlier work an unexpected incidence of late appearing recurrences were observed (mammary carcinoma) but were not confirmed histologically. This is now being done. As part of this, the effect of immune suppression (ALS plus adult thymectomy) will be performed at various times after local irradiation of a fibrosarcoma (MCA induced) to assess the time course of destruction by the immune rejection response of tumor cells not killed by the radiation.